Dermal formulation for granuloma annulare

ABSTRACT

A dermatological formulation or topical preparation containing fine grain bentonite and a lipophilic agent is provided to treat granuloma annulare dermatosis of the skin.

This is a continuation of application Ser. No. 712,434, filed Jun. 10,1991, and now abandoned.

FIELD OF THE INVENTION

This invention relates to the art of treating granuloma annulare (anaffliction of the skin) to return it to its natural healthy softtextured condition without surgery or pain and especially deals with abentonite-lipophilic agent, dermatological formulation, or topicalpreparation to homeopathically reverse the granulomatous process ofgranuloma annulare without risking infection, scarring or disfigurement.

BACKGROUND OF THE INVENTION

Granuloma annulare (G.A.) is a dermatosis of unknown cause characterizedby papules that are usually present in an annular configuration. It hasbeen reported to follow insect bites, sun exposure and trauma. Somecases appear to be due to hereditary predisposition since the lesionshave occurred in identical twins and siblings as well as in more thanone generation of patients. It is usually idiopathic.

The most common type of G.A. occurs in children and young adults.Lesions are usually asymptomatic, skin-colored, erythematous orviolaceous, well defined, dome shaped papules often arranged in acomplete or half circle. Solitary lesions may also be present. Lesionsare most commonly seen on the dorsa of the hands and feet, but mayappear on the forearms, arms, lower legs, and thighs. The face and scalpare rarely affected.

Other types of G.A. include a variant with larger, deep, dermal orsubcutaneous nodules which may occur on the palms, legs, buttocks orscalp. The perforating type of G.A. manifests itself as small papuleswith central umbilication. These lesions are most frequently reported tooccur on the hands and fingers. A more rarely encountered variant ofG.A. presents as circinate erythematous lesions usually on the trunk. Inolder adults, the disseminated form of G.A. is more commonly seen.Hundreds to thousands of individual papules arise anywhere on the skinbut with usual marked involvement of the trunk.

Patients with G.A. are generally healthy. Recently, the disseminatedform of G.A. has been seen more frequently in patients who areserologically HIV positive. Otherwise, laboratory tests are usuallynormal. The chief laboratory aid in the diagnosis of G.A. is the skinbiopsy. Intradermal foci of granulomatous inflammation are detectedwhich have a central core of incomplete, reversible necrosis(necrobiosis) of collagen surrounded by a wall of palisaded histiocytesintermingled with a few acute inflammatory cells. All variants manifesta similar histopathologic finding but the perforating variant also hascentral lesion ulceration and communication between the area ofnecrobiosis and the skin surface.

Granulomas are generally formed by the accumulation of monocytes which,upon proper stimulation, develop into macrophages and may furtherdevelop into foreign body multinucleated giant cells. The stimulationcausing these developments may come from microorganisms, from locallydamaged tissue or from foreign material that is introduced into thebody. It is known that cutaneous granulomas can result from thecontamination of wounds with particles of soil or glass which containsilicon dioxide (silica).

Although the disease has been reported to spontaneously resolve in twoyears, lesions tend to be recurrent and usually at the originallyinvolved site. Resolution of recurrent lesions have been reported tooccur within another three years.

A wide array of treatment modalities has been employed to hasten theresolution of lesions. These include X-ray therapy, cryotherapy,surgical incision and excision, skin grafting, and intralesionalinjections of corticosteroids. All such treatment methods are invasiveand entail risks of secondary infection, scarring and disfigurement.Orally administered salicylates, antimalarials, dapsone andcorticosteroids have also been used. These medications are not withoutpotential and dangerous sequelae. Of all these surgical and medicaltreatments, only the intralesional injection of corticosteroid is saidto be of any benefit. However, these injections are painful and mayresult in disfiguring cutaneous atrophy of the injected areas.

It would therefore be an improvement in this art to provide a bentonitecontaining dermal formulation or topical preparation for reversing thegranulomatous process of granuloma annulare.

Specifically, it would be an improvement in this art to provide asynergistic, small particle size bentonite-lipophilic agent formulationto safely reverse the granulomatous process of granuloma annulare.

SUMMARY OF THE INVENTION

According to this invention, there is provided a dermatologicalformulation or topical preparation for treating granuloma annularedermatosis. This formulation or preparation contains small particlesized bentonite, a lipophilic carrier agent, a diluent if needed tocontrol viscosity, and a preservative if needed to prevent microbialgrowth.

Bentonite is composed of the clay mineral montmorillomite and is ahydrous aluminum silicate. It is an inorganic, non-toxic, non-irritatingchemical with the approximate chemical formula (Al, Fe₁.67 Mg₀.33) Si₄O₁₀ (OH)₂ (Na⁺, Ca⁺⁺ ₀.33).

The bentonite can be a commercially available, U.S.P. grade such as theone having the following analysis as expressed in oxides:

    ______________________________________                                        Silicon dioxide  67.60%                                                       Aluminum oxide   14.30                                                        Calcium oxide    1.85                                                         Magnesium oxide  1.70                                                         Sodium oxide     1.58                                                         Ferric oxide     1.08                                                         Potassium oxide  1.03                                                         Ignition loss    10.86                                                                         100.00%                                                      ______________________________________                                    

A useful bentonite also has the following typical properties:

    ______________________________________                                        Viscosity (5% suspension in water)*                                                                     150 cps                                             Acid Demand               2.6                                                 Total plate count (aerobic microbes/g)                                                                  100 max                                             Aluminum/Magnesium ratio  5.0                                                 Moisture                  8.0 (max)                                           Dry particle size (finer than 200 mesh,                                                                 90%                                                 (74 microns))                                                                 pH (5% dispersion in water)                                                                             9.0-10.0                                            ______________________________________                                         *Viscosity is very dependent on particle size and size distribution, and      can be higher (up to and over 800 centipoise) for other grades of             bentonite.                                                               

The bentonite is preferably colloidal and preferably has a micron sizeup to 100 microns although larger sizes of, say, up to 500 microns, maybe useful. Large granules of bentonite are not effective and mayactually aggravate the granuloma annulare dermatosis.

The carrier portion of the formulation must be a lipophilic agent sothat the bentonite will be percutaneously absorbed into the skin.

In general, the lipophilic agent is an agent of low viscosity to beeasily spreadable on the skin, preferably odorless, with a melting pointof preferably about 3° C. to be spreadable at room temperatures. Anyester of a long chain saturated fatty acid would be acceptable providedit has a low viscosity and is odorless. The carrier must be sufficientlyliquid or dilutable enough to make the end product spreadable.

Examples of suitable lipophilic carriers are agents such as:

    ______________________________________                                        U.S.P. cold cream                                                                           Glycerin                                                        Petroleum jelly                                                                             Aquaphor ®                                                                           }(manufactured by                                                             Beirsdorf, Inc.                                      Vegetable oils                                                                              Eucerin ®                                                                            }P.O. Box 5529,                                                               Norwalk, CT                                                                   06856-5529)                                          Olive oil     Animal fats such as lanolin                                     Mineral oil   and anhydrous lanolin                                           Polyethylene glycols                                                                        Hydrocarbons                                                    Propylene glycol                                                                            Waxes                                                           ______________________________________                                    

Viscosity of the product can be controlled by the addition of an alcoholsuch as ethanol, butanol, propanol, 2-hydroxy propane, and the like.

The preservative material can be any one of a number of non-toxicpreservatives such as benzoic acid, methylparaben or the like.

Use of even a preferred amount of bentonite without the lipophiliccarrier can create xerosis of the cutis thereby aggravating thegranuloma annulare affliction.

It is believed that unobvious synergistic interaction of the fine micronsize bentonite and the lipophilic carrier occurs since the bentonite,without this carrier, causes aggravation of the affliction. Thebentonite must be percutaneously absorbed and must have a small particlesize to create the homeopathical healing.

A general formulation according to my invention includes the followingparts by weight:

    ______________________________________                                        Fine particle size Bentonite                                                                        20-60%                                                  Ester of long chain saturated fatty acid                                                            20-80%                                                  Alcohol to control viscosity                                                                         0-20%                                                  Preservatives such as methylparaben                                                                  0-0.1%                                                 A preferred formulation in parts by weight is as follows:                     Native hydrated aluminum silicate                                                                    30%   }(particle sizes                                 Native colloidal hydrated aluminum                                                                   20%   }of not more                                     silicate                     }than about 100                                                               }microns)                                        Tetradecanoic acid, 1-methylethyl ester                                                              40%                                                    2-hydroxypropane       10%                                                    4-hydroxy benzoic acid, methylethyl ester                                                           0.1%                                                    ______________________________________                                    

The above preferred formulation was used to treat six patients havinggranuloma annulare dermatosis. A dab of the formulation was gentlyrubbed onto the afflicted areas of the patient's skin daily for 2-6weeks. After treatment, the lesions were no longer detected in all ofthe patients.

Bentonite is a native colloidal hydrated aluminum silicate which hashigh absorbent properties and has been used as an ingestant for thetreatment of diarrhea and also used in various cosmetics. It is not atoxic substance and thus safe for such usage. While bentonite has beenshown to induce the formation of granulomas when injected intolaboratory animals, I have contrary to the teachings of the prior art,developed a successful topical application of bentonite in a lipophiliccarrier to reverse the granulomatous process safely via a homeopathiceffect.

I have applied my topical preparation on patients having long standingareas with granuloma annulare and have carefully noted the resolution ofthe lesions at the sites of application.

I believe that the silicate portion of the aluminum silicate (bentonite)molecule mediated the resolution, although the aluminum is possibly alsoinvolved in this process. I believe that the active reactant may inhibitan intracellular biochemical reaction of the monocyte that is requiredfor the differentiation of this cell into a macrophage. The reactant mayinterfere with the recruitment of monocytes into the affected areas orit may inhibit the phagocytic action of the macrophages through someother intracellular or intercellular biochemical interaction.Alternatively, if the collagen has a defect which induces the granulomaformation, the colloidal bentonite particles may coat the affectedcollagen fibers and mask their putative ability to stimulate theformation of granulomas.

From the above descriptions it will be understood by those skilled inthe art that my formulation causes fine grain bentonite to penetrategranuloma annulare affected areas of human skin without any side effectsand create a homeopathic reversal of the granulomatosis processpermitting the skin to return to a healthy, soft textured condition.

I claim as my invention:
 1. The method of homeopathic treatment ofgranuloma annulare dermatosis which comprises topically administering tothe areas of a human patient's skin afflicted by granuloma annularedermatosis a formulation containing fine grain bentonite having a grainsize up to 500 microns dispersed in a spreadable lipophilic agent,rubbing the formulation on the skin to expedite percutaneous absorptionof the formulation into the skin to establish a homeopathic reversal ofthe granuloma annulare affliction, and repeating the topicaladministration of the formulation as needed.
 2. A method of decreasingthe lesions of granuloma annulare on a human patient's skin whichcomprises rubbing into the afflicted areas of the skin a topicalformulation comprising 20-60% by weight fine grain colloidal bentonitehaving a particle size of not more than about 100 microns, 20-80% byweight of an ester of long chain saturated fatty acids, up to 20% byweight alcohol, up to 0.1% by weight of a preservative and with saidbentonite uniformly dispersed in said ester and continuing rubbing saidformulation into the skin without irritation until it is percutaneouslyabsorbed by the skin.
 3. The method of claim 1 wherein the topicaladministration is carried out at room temperature.
 4. A topicalpreparation for homeopathic treatment of granuloma annulare dermatosiswhich comprises 20-60% by weight fine grain bentonite composed of about30% by weight native hydrated aluminum silicate and 20% by weight nativecolloidal hydrated aluminum silicate, 20-80% by weight of an ester oflong chain saturated fatty acids, up to 20% by weight alcohol, up to0.1% by weight preservative, said bentonite having a particle size ofnot more than about 100 microns and uniformly dispersed in said ester,said ester comprising tetradecanoic acid, 1 methylethyl ester, and saidpreparation adapted to be rubbed on the skin of a granuloma annulareinfected person to be percutaneously absorbed without irritation.